Is BFSP1 p.Ala42Val (c.125C>T) pathogenic?

BFSP1 p.Ala42Val (c.125C>T) is classified Uncertain significance in BFSP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-18). AlphaMissense: likely benign (0.1322); Ultra-rare (popmax 0.017%, nfe); Associated with cataract 33.

What condition is associated with BFSP1 p.Ala42Val (c.125C>T)?

BFSP1 p.Ala42Val (c.125C>T) is associated with cataract 33 (ClinVar).

How common is BFSP1 p.Ala42Val (c.125C>T) in the general population?

BFSP1 p.Ala42Val (c.125C>T) is ultra-rare (popmax 0.017%, nfe) (gnomAD).

What do computational predictors say about BFSP1 p.Ala42Val (c.125C>T)?

AlphaMissense predicts likely benign (score 0.1322) — an in-silico prediction, not a clinical call.

BFSP1 p.Ala42Val

c.125C>T · VCV3665755

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1322 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.017%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

cataract 33

Computational evidence

Protein change
AlphaMissense	0.1322	likely benign
REVEL	0.456	indeterminate
SaProt	LLR -8.55	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -1.1, phastCons 0.95
Regional constraint	o/e 0.97	unconstrained · MANE · 37 kb · p 0.4 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.017% European (non-Finnish) · 176/1,034,584 alleles

Filtering AF 0.0149% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0141%

Overall 0.0137% 180/1,317,686 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.017%	5,878
African / African-American	0.00309%	32,339
Finnishnot grpmax-eligible	0.00268%	37,370
Remaining individualsnot grpmax-eligible	0.00205%	48,724

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BFSP1
Protein: p.Ala42Val
Coding: c.125C>T
MANE Select: NM_001195
Type: single nucleotide variant
Location: chr20:17531205 (GRCh38)
Gene constraint: LOEUF 1.371 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.66
Residue 42: a functional site (cleavage); a modified residue (n-acetylalanine); the if rod domain; the 'coil 1a' region

Full BFSP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cataract 33 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BFSP1 p.Ala643Thr Uncertain significance ★★ ⚠ same condition
BFSP1 p.Arg560Cys Uncertain significance ★★ ⚠ same condition
BFSP1 p.Arg69Trp Uncertain significance ★★ ⚠ same condition
BFSP1 p.Asp19Asn Uncertain significance ★★ ⚠ same condition
BFSP1 p.Gln294Arg Uncertain significance ★★ ⚠ same condition
BFSP1 p.Gly46Trp Uncertain significance ★★ ⚠ same condition
BFSP1 p.Ile271Thr Uncertain significance ★★ ⚠ same condition
BFSP1 p.Leu68Phe Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/bfsp1-p-ala42val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown